title: Universal anti-neuraminidase antibody inhibiting all influenza A subtypes.
abstract: The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues I222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses.
authors.affiliation: Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology and Emerging Pathogens Research Centre, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Doyle
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Hashem
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.forename: Gary
authors.initials: G
authors.lastname: Van Domselaar
authors.forename: Louise
authors.initials: L
authors.lastname: Larocque
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Daryl
authors.initials: D
authors.lastname: Smith
authors.forename: Terry
authors.initials: T
authors.lastname: Cyr
authors.forename: Aaron
authors.initials: A
authors.lastname: Farnsworth
authors.forename: Runtao
authors.initials: R
authors.lastname: He
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
authors.forename: Earl G
authors.initials: EG
authors.lastname: Brown
authors.forename: Xuguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D056738:Cross Protection; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Cross-protection; Neuraminidase; Universal antibody